Cytotechnology

, Volume 24, Issue 2, pp 99–108

Alteration of mammalian cell metabolism by dynamic nutrient feeding

  • Weichang Zhou
  • Jutta Rehm
  • Anna Europa
  • Wei-Shou Hu
Article

DOI: 10.1023/A:1007945826228

Cite this article as:
Zhou, W., Rehm, J., Europa, A. et al. Cytotechnology (1997) 24: 99. doi:10.1023/A:1007945826228

Abstract

The metabolism of hybridoma cells was controlled to reduce metabolic formation in fed-batch cultures by dynamically feeding a salt-free nutrient concentrate. For this purpose, on-line oxygen uptake rate (OUR) measurement was used to estimate the metabolic demand of hybridoma cells and to determine the feeding rate of a concentrated solution of salt-free DMEM/F12 medium supplemented with other medium components. The ratios among glucose, glutamine and other medium components in the feeding nutrient concentrate were adjusted stoichiometrically to provide balanced nutrient conditions for cell growth. Through on-line control of the feeding rate of the nutrient concentrate, both glucose and glutamine concentrations were maintained at low levels of 0.5 and 0.2 mM respectively during the growth stage. The concentrations of the other essential amino acids were also maintained without large fluctuations. The cell metabolism was altered from that observed in batch cultures resulting in a significant reduction of lactate, ammonia and alanine production. Compared to a previously reported fed-batch culture in which only glucose was maintained at a low level and only a reduced lactate production was observed, this culture has also reduced the production of other metabolites, such as ammonium and alanine. As a result, a high viable cell concentration of more than 1.0 × 107 cells/mL was achieved and sustained over an extended period. The results demonstrate an efficient nutrient feeding strategy for controlling cell metabolism to achieve and sustain a high viable cell concentration in fed-batch mammalian cell cultures in order to enhance the productivity.

Oxygen uptake rate hybridoma cells fed-batch culture dynamic nutrient feeding cell metabolism salt-free nutrientconcentrate 

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Weichang Zhou
    • 1
  • Jutta Rehm
    • 1
  • Anna Europa
    • 1
  • Wei-Shou Hu
    • 1
  1. 1.Department of Chemical Engineering and Materials ScienceUniversity of MinnesotaMinneapolisUSA
  2. 2.Merck Research LaboratoriesMerck & Co., Inc.Rahway

Personalised recommendations